The purposes of this research program are to determine the interrelationship of glucose stimulation, of insulin release and other insulin secretagogues on the acute uptake and efflux of 45Ca from isolated rat islets; utilize the digestion filtration technique for mass isolation of rat islets for use in obtaining purified plasma membrane and other subcellular fractions of the islets; utilize these subcellular fractions for studies on the effect of glucose on calcium content, binding and transport by the subcellular fractions; determine the effect of glucose and other agents on the uptake and efflux of 65Zn in isolated rat islets; determine the content, binding and transport of 65Zn in subcellular fractions of the islets. The uptake and efflux of 45Ca and 65Zn by isolated rat islets is determined by the dual-isotope technique. Studies have been completed on the acute effect of D-glucose on the uptake and efflux of 45Ca in the presence and absence of insulin release and studies are to be accomplished on the effect of alpha and beta anomers of D-glucose, tolbutamide, amino acids, agents that affect the cAMP content of the islets, cytochalasin B and D, antimicrotubular agents and somatostatin. Studies are in progress on the uptake and efflux of 65Zn using isolated rat islets.